It is proposed to utilize the pH stat technique to study the process by which isolated segments of small intestine from the urodele, Amphiuma, alkalinize the mucosal media - a process which will be referred to as bicarbonate secretion. Sheets of small intestine will be mounted between halves of a lucite chamber that exposes 10.7 cm2 of stripped mucosa to 10 ml of oxygenated unbuffered media on its mucosal surface and a larger volume of the same media on its serosal surface. In other experiments a serosal solution containing 25 mM HCO3- gassed with a 95% O2, 5% CO2 mixture (pH 7.4) will be employed on the serosal side. The mucosal pH will be statted to 7.4 with an automatic titrator while the transmural potential is clamped at zero. The influence on base secretion of several metabolic agents (glucose, glutamine, 2-deoxyglucose, dinitrophenol, acetazolamide), transport effectors (ouabain, SITS) ion replacements (Na ion, Cl-) and theophylline will be examined in the presence and absence of serosal HCO3- and CO2. In addition the labelled unidirectional fluxes of Na ion and Cl- will be measured in paired adjacent segments in which HCO3- secretion is measured simultaneously. This study will aid in defining the role of metabolism in HCO3- secretion, the role of HCO3- secretion in the transport of other electrolytes and the behavior of base secretory processes during the development of pathological secretory states such as cholera.